Inferring Compensatory Kinase Networks in Yeast using Prolog

George A. Elder
(Queen Mary University of London)
Conrad Bessant
(Queen Mary University of London)

Signalling pathways are conserved across different species, therefore making yeast a model organism to study these via disruption of kinase activity. Yeast has 159 genes that encode protein kinases and phosphatases, and 136 of these have counterparts in humans. Therefore any insight in this model organism could potentially offer indications of mechanisms of action in the human kinome. The study utilises a Prolog-based approach, data from a yeast kinase deletions strains study and publicly available kinase-protein associations. Prolog, a programming language that is well-suited for symbolic reasoning is used to reason over the data and infer compensatory kinase networks. This approach is based on the idea that when a kinase is knocked out, other kinases may compensate for this loss of activity. Background knowledge on kinases targeting proteins is used to guide the analysis. This knowledge is used to infer the potential compensatory interactions between kinases based on the changes in phosphorylation observed in the phosphoproteomics data from the yeast study. The results demonstrate the effectiveness of the Prolog-based approach in analysing complex cell signalling mechanisms in yeast. The inferred compensatory kinase networks provide new insights into the regulation of cell signalling in yeast and may aid in the identification of potential therapeutic targets for modulating signalling pathways in yeast and other organisms.

In Enrico Pontelli, Stefania Costantini, Carmine Dodaro, Sarah Gaggl, Roberta Calegari, Artur D'Avila Garcez, Francesco Fabiano, Alessandra Mileo, Alessandra Russo and Francesca Toni: Proceedings 39th International Conference on Logic Programming (ICLP 2023), Imperial College London, UK, 9th July 2023 - 15th July 2023, Electronic Proceedings in Theoretical Computer Science 385, pp. 260–273.
Published: 12th September 2023.

ArXived at: https://dx.doi.org/10.4204/EPTCS.385.26 bibtex PDF
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